Inorganic pyrophosphate (PPi) is released from both lapine and canine immature and adult hyaline cartilage and fibrocartilage maintained in short-term organ culture. These tissues also release proteoglycans as measured by hexuronic acid. The release of both substances is highly correlated and is blocked by freeze-thawing the tissues before culture. Experiments are in process (1) to ascertain the effect on PPi release of blocking proteoglycan synthesis and (2) to extend the work to normal and osteoarthritic human cartilage. Triclinic calcium pyrophosphate dihydrate (CPPD) were synthesized that uniformly incorporate 45Ca and 85Sr. After injection into rabbit joints, the rate of clearance of nuclide were followed by external counting. Such crystals were phagocytosed by fixed synovial macrophage-like cells. Clearance rates were not affected by the induction of profound hypomagnesia by dietary deprivation of magnesium (intracellular magnesium remains normal) but were affected by synovial hemosiderosis or the induction of hypothyroidism. The intracellular clearance mechanism will now be examined in detail in cultured synovial cells incubated with labelled CPPD crystals. Sodium urate, CPPD, silica and apatite crystals all adsorb IgG. Urate appears to adsorb IgG with Fc moiety functionally exposed. Many of the biological properties of urate crystals are attributable to the adsorbed IgG. The fate of the IgG adsorbed to crystals phagocytosed by neutrophils is now being studied.